BIOCHEMICAL BASIS FOR CISPLATIN AND 5-FLUOROURACIL SYNERGISM IN HUMAN OVARIAN-CARCINOMA CELLS
BIOCHEMICAL BASIS FOR CISPLATIN AND 5-FLUOROURACIL SYNERGISM IN HUMAN OVARIAN-CARCINOMA CELLS
复制标题
DOI：
10.1073/pnas.83.23.8923
复制
发表时间：
1986-12-01
影响因子：
11.1
通讯作者：
PRIEST, DG
中科院分区：
文献类型：
--
作者：
SCANLON, KJ;NEWMAN, EM;PRIEST, DG
将人卵巢细胞系A2780暴露于顺铂（10 μ M）或5-氟尿嘧啶（5-FUra）（5 μ M）1小时。单独使用任一药剂的细胞毒性均低于14%。顺铂（10 μ M）和5 FUra（5 μ M）组合1小时导致细胞生长减少76%。胸苷（dThd，10 μ M）如果与顺铂和5 FUra的组合同时给予，则完全保护肿瘤细胞。暴露于顺铂30分钟增加了细胞内的5，10-亚甲基四氢叶酸和四氢叶酸2.5倍。完整细胞形成5-氟脱氧尿苷酸（FdUMP）-胸苷酸（dTMP）合成酶复合物的能力，当与氟脱氧尿苷（FdUrd）孵育时，增强2.5倍，当细胞用顺铂预处理。这些实验表明，顺铂可以增加FdUMP与dTMP合酶紧密结合所必需的还原叶酸的可用性，从而增强顺铂和5 FUra组合的细胞毒性。
The human ovarian cell line A2780 was exposed to either cisplatin (10 .mu.M) or 5-fluorouracil (5FUra) (5 .mu.M) for 1 hr. Cytotoxicity was less than 14% with either agent alone. Cisplatin (10 .mu.M) and 5FUra (5 .mu.M) in combination for 1 hr caused a 76% reduction in cell growth. Thymidine (dThd, 10 .mu.M), if given concomitantly with the combination of cisplatin and 5FUra, completely protected the tumor cells. A 30-min exposure to cisplatin increased the intracellular pools of 5,10-methylenetetrahydrofolate and tetrahydrofolate 2.5-fold. The capacity of intact cells to form 5-fluorodeoxyuridylate (FdUMP)-thymidylate (dTMP) synthase complex when incubated with fluorodeoxyuridine (FdUrd) was enhanced 2.5-fold when the cells were pretreated with cisplatin. These experiments demonstrate that cisplatin can increase the availability of the reduced folate necessary for tight binding of FdUMP to dTMP synthase, thus enhancing the cytotoxicity of the cisplatin and 5FUra combination.